Organ systems such as heart, muscle and nerve derive their essential excitability due to the presence of voltage-dependent, cation-selective channels in their cell membranes. Employing structurally described, cation-selective channels incorporated into lipid micelles where no complications arise due to electrochemical potentials and also channels incorporated into vesicles, the objectives of this supplement are: 1) to experimentally determine binding constants and rate constants for ion interactions with channels by cation nuclear magnetic resonance, 2) to utilize the experimental binding and rate constants in calculating single channel currents by means of Eyring rate theory to introduce voltage dependence to the NMR-derived rat constants with the purpose of obtaining the free energy profiles for ion movement through the channel, and 3) to determine the underlying energy components of the free energy profiles for ion movement through the channel for the purpose of developing a detailed understanding of the factors responsible for ion selectivity. The channels to be studied in this manner include a number of derivatives and analogues of gramicidin and of the synthetic voltage dependent channel, HCO(-Ala-Ala-Gly)5OMe. The ions to be studied include 7Li, 23Na, 39K, 87Rb, 133Cs, 109Ag, 205Tl, 43Ca and 137Ba, and the lipids are to be varied to determine the effects of the polar head groups and of the structure of the hydrocarbon chains. Recognizing that the excitability of cell membranes and its consequences are fundamental to the definition of living systems and that the loss of the resulting electrical signals from the heart and brain are utilized in the definition of death, the development of the principles underlying the excitability of cell membranes achieves a certain prominence and the search for the molecular basis for ion selective transport a certain sense of significance.